This project investigates the hypothesis that malfunctions of the primate frontal cortex are related to behavioral deficits characteristic of schizophrenia by testing human schizophrenic patients, their first degree relatives, and other patients populations (Part A), and by testing monkeys with experimental lesions of frontal cortex (Part B). Both parts use diverse batteries of behavioral tasks. Oculomotor tasks involving tracking and spatial memory and attention are emphasized because smooth pursuit eye movements and saccadic eye movements in delayed-response and attentional paradigms are both impaired in human schizophrenics and in monkeys with frontal lesions. The proposed tasks will analyze established deficits into their constituent or underlying mechanisms, search for additional deficits, and bear on the more specific hypothesize that a disruption of the ability to guide behavior with internal representations is an essential aspect both of schizophrenia and of behavior following frontal lobe lesions. Human subjects will include schizophrenic patients, relatives of schizophrenics, and patients with frontal lobe lesions, as well as appropriate controls for each of these groups. Experiments will include investigations of (1) working memory using the oculomotor delayed- response task, (2) spatial deployment of attention, (3) saccadic disinhibition using express saccade tasks and (4) the generation of saccades opposite to targets in the antisaccade task. The smooth pursuit eye movements of all subjects will also be tested in order to analyze whether the well-documented ocular tracking disorders of schizophrenics and their first degree relatives are correlated with deficits concerning the inhibition of responses, representational memory, and spatial attention. Monkey frontal lobe lesions will be (1) arcuate sulcus, including the smooth pursuit representation in the fundal region of the arcuate frontal eye field (FEF), (2) dorsomedial prefrontal cortex, including the supplementary eye field (SEF), and (3) dorsolateral prefrontal cortex (dlPFC) adjacent to these eye fields. Lesions will be unilateral in order to assess the directionality of deficits; however, most monkeys will receive two or more serial lesions involving both hemispheres. The smooth pursuit deficits of monkeys with FEF lesions will be analyzed in several ways to further comparison with the schizophrenic tracking disorder. Likewise, the saccadic deficits of monkeys with FEF, SEF, and dlPFC lesions will be quantified and analyzed, with emphasis on comparisons with behavior in schizophrenics. The effects of dopamine agonists and antagonists will also be tested in these same monkeys, before and after their lesions, to assess the contribution of dopaminergic systems to these behaviors and structures. Neuroanatomical experiments will ascertain the differential connectivity of the saccadic and smooth pursuit sectors of the monkey's FEF.